AVAnT1A study: Investigating early COVID-19 vaccination and type 1 diabetes risk in children

Type 1 diabetes is an autoimmune disease that leads to disrupted glucose metabolism. It requires lifelong insulin therapy. The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) collaborates within a European network to develop new methods to prevent this condition which is, to date incurable. AVAnT1A is GPPAD's third intervention study. It will investigate whether vaccination against SARS-CoV-2 in the first year of life can protect children who have an increased genetic risk for type 1 diabetes from developing the condition. The study is supported by funding from The Leona M. and Harry B. Helmsley Charitable Trust.

In Germany, four out of 1000 children are diagnosed with type 1 diabetes, a metabolic disorder triggered by an autoimmune reaction. In individuals with type 1 diabetes, the immune system destroys the insulin-producing cells in the Langerhans islets of the pancreas. Affected individuals require lifelong insulin treatment as insulin plays a vital role in transporting sugar from the blood into the body's cells. Approximately 90 percent of affected children and adolescents have no close relatives with type 1 diabetes, often leading to a late and unexpected diagnosis. However, researchers can identify the underlying autoimmune process long before symptoms occur, based on islet autoantibodies in the blood.

Viral infections are an environmental factor for type 1 diabetes

The exact causes of the underlying autoimmune reaction remain unclear. In large-scale, long-term studies, researchers at Helmholtz Munich have identified viral infections in early childhood as a crucial environmental factor for the development of type 1 diabetes. During the COVID-19 pandemic, GPPAD researchers made another important observation: after contracting a SARS-CoV-2 infection, children with an increased risk for type 1 diabetes were more likely to develop islet autoantibodies.

COVID-19 has increased the risk of the disease. We have seen that children who had COVID-19 before age 18 months were around five times more likely to develop the islet autoantibodies as those who were not infected."

Prof. Ezio Bonifacio, GPPAD researcher at the Center for Regenerative Therapies Dresden (CRTD) of TUD Dresden University of Technology

These autoantibodies are biomarkers indicating the beginning of the autoimmune process that leads to type 1 diabetes.

New study aims to clarify correlation

In a new study, GPPAD aims to further investigate this relationship. The AVAnT1A Study - short for "AntiViral Action against Type 1 Autoimmunity" - examines whether vaccination against COVID-19 at the age of six months can prevent the development of islet autoantibodies in babies at increased genetic risk of developing type 1 diabetes, thus reducing their risk of developing the condition. The vaccine used is safe and approved for children aged six months and older. The participating children are randomly assigned to two groups beforehand using a randomized, placebo-controlled study design. The intervention group will receive the COVID-19 vaccine, the control group will receive a placebo injection without active ingredients. The vaccine is provided by the Center for Pandemic Vaccines and Therapeutics (ZEPAI) at the Paul-Ehrlich-Institute, Federal Institute for Vaccines and Biomedicines. Additionally, the study is double-blinded, so the researchers, the study personnel, and the families, will not know which group a child belongs to until the study is completed.

"Since many infections in young children occur almost without symptoms, we also ask participating families to collect saliva and stool samples from their children at regular intervals," explains Prof. Anette-Gabriele Ziegler, Director of the Helmholtz Munich Institute for Diabetes Research and GPPAD, Chair of Diabetes and Gestational Diabetes at Klinikum rechts der Isar and Technical University of Munich. From these samples, researchers can identify which viruses the children had contact with. This allows the researchers to clarify further connections between type 1 diabetes and viral infections in early childhood.

"With a planned number of 2252 participants, the AVAnT1A Study is the largest intervention study to date exploring the relationship between type 1 diabetes and early childhood viral infections. Insights generated with this study will help us to move closer to our goal of a world without type 1 diabetes," says Prof. Sandra Hummel, lead scientist in the AVAnT1A study and researcher at Helmholtz Munich. Children with an increased genetic risk for developing type 1 diabetes are invited to participate in the AVAnT1A study. Their increased risk is detected within the newborn screening called "Freder1k", which for Germany is offered in Bavaria, Lower Saxony, Saxony, and Thuringia. Parents can test their newborns either directly at the birth clinic or in the pediatrician's office until six weeks of age. A tiny drop of blood from the umbilical cord or heel is sufficient for this test.

Children participating in the AVAnT1A study are invited for regular check-ups until their sixth birthday. The families benefit from participating in an early detection program for type 1 diabetes. If a child shows initial signs of the autoimmune disease, this can be detected early in the disease progression, ensuring families access to optimal support and information to support their child.

"This study holds promise to help tease out the link between viral infections and the development of autoimmunity in type 1 diabetes;" says Anne Koralova, Program Officer at the Helmsley Charitable Trust. "The investigators at GPPAD have done incredible work studying strategies to prevent the development of type 1 diabetes, and Helmsley is committed to supporting these innovative studies."

AVAnT1A is GPPAD's third study

Following the POInT Study (short for: Primary Oral Insulin Trial) and the SINT1A Study (short for: Supplementation with B. INfantis for Mitigation of Type 1 Diabetes Autoimmunity), AVAnT1A is now GPPAD's third intervention study aimed at developing new preventive measures for type 1 diabetes. The POInT Study investigated whether the administration of insulin powder in the first three years of life has a protective effect on the immune system. The study will be completed in 2024. Participants in the SINT1A Study receive a probiotic in the first year of life, which aims to positively influence the microbiome and thus prevent autoimmune reactions. The SINT1A study achieved full recruitment in March 2024. The GPPAD research platform, and all studies supported within it, are financed by The Leona M. and Harry B. Helmsley Charitable Trust in the U.S.